Abstract
BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing synaptonemal complexes. Like BRCA1 and RAD51, BRCA2 relocates to PCNA+ replication sites following exposure of S phase cells to hydroxyurea or UV irradiation. Thus, BRCA1 and BRCA2 participate, together, in a pathway(s) associated with the activation of double-strand break repair and/or homologous recombination. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Antibodies, Monoclonal
- BRCA1 Protein / analysis
- BRCA1 Protein / metabolism*
- BRCA2 Protein
- Breast Neoplasms / genetics
- Breast Neoplasms / pathology*
- Cell Line
- Cell Nucleus / ultrastructure
- Chromosome Mapping
- DNA Damage
- DNA Repair
- DNA Replication
- DNA-Binding Proteins / analysis
- DNA-Binding Proteins / genetics
- Female
- Genes, BRCA1*
- Genes, Tumor Suppressor*
- Humans
- Meiosis
- Mitosis
- Neoplasm Proteins / analysis
- Neoplasm Proteins / genetics*
- Neoplasm Proteins / metabolism*
- Ovarian Neoplasms / genetics
- Rad51 Recombinase
- Transcription Factors / analysis
- Transcription Factors / genetics*
- Transcription Factors / metabolism*
- Transfection
- Tumor Cells, Cultured
- Zygote / cytology
Substances
- Antibodies, Monoclonal
- BRCA1 Protein
- BRCA2 Protein
- DNA-Binding Proteins
- Neoplasm Proteins
- Transcription Factors
- RAD51 protein, human
- Rad51 Recombinase